Evaluation of the effects of diazepam and an experimental anti-anxiety drug on regional cerebral blood flow.

In the normal brain, cerebral blood flow (CBF) and function are closely coupled. Thus, changes in brain function associated with drug-induced anxiety reduction should be accompanied by parallel CBF changes. Benzodiazepines such as diazepam have been reported to reduce CBF. It is unclear, however, if this CBF decrease is specifically a function of the anti-anxiety property of the drug. To examine the relationship between drug-induced anxiety reduction and CBF changes more closely, i.v. injections of an established anxiolytic agent and an experimental anti-anxiety drug were given to patients with generalized anxiety disorder. CBF and anxiety levels were measured before and 30 min after i.v. administration of diazepam (0.12 mg/kg), ondansetron (0.24 mg/kg), and normal saline during separate visits to the laboratory. The order of drug administration was randomized, and the injections were given under double-blind conditions. Diazepam but not ondansetron or saline reduced anxiety. Global CBF reduction was seen after diazepam, but no changes were found following the other two experimental conditions. The CBF values were adjusted for test-retest changes in carbon dioxide levels. Postdiazepam decreases in CBF and anxiety levels did not correlate.